Experimental rationale for the therapeutic use of neurotrophins in amyotrophic lateral sclerosis

Jeffrey L. Seeburger, Joe E. Springer

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Current therapeutic efforts to treat chronic and progressive neurodegenerative disease include, for the first time, attempts to regenerate affected nervous tissue using neurotrophic factors. The rationale for using trophic factors includes the understanding that they support neuronal survival and regrowth processes. The potential benefits of trophic factor therapy will be no more realized in the near future than in the treatment of amyotrophic lateral sclerosis (ALS). ALS is pathologically characterized by the selective degeneration of specific populations of cranial and spinal motoneurons. Evidence for the existence of factors that support motoneurons has come from studies demonstrating that motoneurons receive trophic influences from various tissues, both central and peripheral, within their local environment. Although the identity of these putative tissue-derived factors has remained enigmatic, recent studies have demonstrated that several previously characterized trophic factors exhibit trophic influences on motoneurons. Among these are several members of the neurotrophin family, most notably brain-derived neurotrophic factor. These neurotrophins meet most of the criteria to be considered motoneuron trophic factors: They are locally available to motoneurons in vivo; motoneurons express specific receptors for these factors; and exogenous application of these factors mimicks the effects of the uncharacterized endogenous agents. The clinical use of these factors for the treatment of ALS, therefore, appears to be scientifically justified.

Original languageEnglish
Pages (from-to)64-72
Number of pages9
JournalExperimental Neurology
Volume124
Issue number1
DOIs
StatePublished - Nov 1993

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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